Process of stabilizing polyvinyl pyrrolidone-iodine compositions



PROCESS OF STABILIZING POLYVINYL PYRROLI- DONE-IODINE COMPOSITIONSWilliam A. Hosmer, Pittsiield, Mass., assignor to General Aniline & FilmCorporation, New York, N. Y., a corporation of Delaware No Drawing.Application September 22, 1954 Serial No. 457,777

1 Claim. (Cl. 16770) This invention relates to a process of stabilizinga dry powdered adduct of iodine and polymeric 1-vinyl-2- pyrrolidone(hereinafter referred to as polyvinyl pyrrolidone) whereby a stablecomposition is obtained which when dissolved in water will not changeits pH and maintain a constant available iodine content.

In the copending application of Herman A. Shelanski, Serial No. 135,519,filed December 28, 1949, now abandonded, there is disclosed a novelcomposition of polyvinyl pyrrolidone and iodine which has been found tobe of substantial value for many applications in which advantage istaken of the bactericidal activity of the iodine but in which theirritating, sensitizing, and toxic properties of the iodine aresubstantially overcome. As disclosed in this application, this noveliodine-polyvinyl pyrrolidone composition may be prepared by adding asolution of iodine, such as Lugols solution or tincture of iodine to anaqueous solution of polyvinyl pyrrolidone followed by dessication in asuitable dryer.

To improve on the method of preparing the foregoing noveliodine-polyvinyl pyrrolidone composition, there is disclosed in thecopending application of Hans Beller and W. A. Hosmer, Serial No.282,458, filed April 15, 1952, now U. S. Patent 2,706,701, a processwhereby dry elemental iodine is mixed with dry powdered polyvinylpyrrolidone. The iodine and powdered polymer is mixed until ahomogeneous powder is obtained, the mixing being carried out inmaterials which are not attacked by iodine so as to avoid theintroduction of metal ions into the finished composition. This mixing iseffected by grinding the iodine and polyvinyl pyrrolidone in a mortarand pestle or more advantageously in a suitable mechanical mixer such asa ball mill. The time of mixing varies only with the efficiency thereof,as the combination of the polyvinyl pyrrolidone with iodine on itssurface is rapid, in fact, such combination will occur to some extent ondropping iodine crystals on the dry powdered polymer.

On completion of the mixing there is obtained a compound in a physicalstate similar to the polymer alone but which contains varyingproportions of available iodine (as distinguished from free iodine),iodide ion, and bound iodine. A distinction between these forms may bemade on an analytical basis, available iodine being determined directlyby dissolving a sample of the product in water and titrating with 0.1-Nsodium thiosulfate solution using starch as an indicator. The amount ofiodine present as iodide ion is determined by reducing the iodinecompound in solution with l-N sodium acid sulfite, adding enough to makethe solution colorless, then adding 0.1-N silver nitrate and enoughnitric acid to make the solution acidic and back-titrating with ammoniumthiocyanate. The iodide ion is the difierence between this figure andthe available iodine as determined above. The total iodine may bedetermined by combustion methods such as that formulated by Hallett inScotts Standard Method of Chemical Analysis, bound iodine then beingdetermined by subtracting the sum of available iodine and iodide ionfrom the total iodine as determined above.

The product thus obtained may have an available iodine content rangingfrom 845% and an iodide ion content from 0.98 to 5.6%. With any givensample of polyvinyl pyrrolidone, the iodine present as available iodineand iodide ion may vary somewhat. On standing, the amount of availableiodine slightly decreases while the amount of iodide ion increases. inorder to obtain a stable product, Hans Beller et al. referred to abovefound that a product in which the ratio of available iodine to iodideion is substantially 2:1 is readily and rapidly obtained by heating thedry blended material in the order of -490 C. Further details regardingthis process may be obtained by reference to their patent, the contentsof which are incorporated herein by reference, especially, the variousiodine-polyvinyl pyrrolidone compositions as prepared in accordance withtheir Examples 1 to V1 inclusive.

The iodine-polyvinyl pyrrolidone compositions prepared in accordancewith the aforestated application form aqueous solutions which containiodine having a very high germicidal activity. The iodine-polyvinylpyrrolidone composition in aqueous solution has a high acid reactionnear a pH of 2, which in some instances, such as, for intravenous use orapplication on sensitive tissue necessitates the adjustment of suchsolution to near neutrality. Solutions so adjusted by alkaline agents,especially sodium bicarbonate have a tendency to lose their availableiodine activity quite rapidly because of the shift of the hydrolysisequation to the right under increasingly alkaline conditions.

When aqueous solutions of iodine-polyvinyl pyrrolidone compositions areprepared and the pH adjusted to neutrality by the addition of sodiumbicarbonate, the available iodine content decreases and the availableiodide ion increases upon storage within a few weeks, thus posing aserious problem when shipping such solutions to hospitals andphysicians. From the time the actual solution is made at the dispensingplant and the time at which it arrives in the hospital or physiciansoflice, which may require several weeks, the solution loses potency inthe available iodine content.

I have discovered that the tendency of the iodine-polyvinyl pyrrolidonecomposition to lose its available iodine content when prepared inaqueous solution. can be very readily overcome by blending 16 to 20parts by weight of sodium bicarbonate per parts by weight of theiodine-polyvinyl pyrrolidone composition having an available iodinecontent from 8 to 15% and an available iodide ion content from 0.98 to5.6% for a period of time ranging from 6 to 36 hours. The resultingproduct is stable and will readily dissolve in water to form essentiallyneutral solutions (having a pH range from 6.6 to 6.9). By thisprocedure, the iodine-polyvinyl pyrrolidone composition is made in amore available and readily useful form for injections and use on mucoustissue.

It is indeed wholly surprising and unexpected that the reactionindicated by the above equation has been found not to occur in the solidstate when sodium bicarbonate is blended with the iodine-polyvinylpyrrolidone composition even though moisture may be present either inthe sodium bicarbonate or the iodine polyvinyl pyrrolidone composition,or both. More surprising is the fact that the solid mixture ofiodine-polyvinyl pyrrolidone composition and sodium bicarbonate has thesame stability as the dry iodine-polyvinyl pyrrolidone compositionalone.

The following example will serve to illustrate how the stabilizediodinepolyvinyl pyrrolidone composition may be prepared in accordancewith the present invention. It is to be understood, however, that thisexample is merely Example I To 100 parts of iodine-polyvinyl pyrrolidonecomposition (made by dry-blending 83.2 parts of polyvinyl pyrrolidonehaving a K value of 30 and 16.8 parts of iodine for 24 hours, followedby 24 hours of heating at 93 C.) there were added 10 parts of anhydroussodium bicarbonate. The mixture was blended for 24 hours in a rotatingglass vessel to insure uniformity. The product was made up as a 1%aqueous solution and had a pH of 6.7 to 6.9. In aging the dry productfor six weeks at 100 F. no change in pH was observed, and no change inthe available iodine and iodide ion content was noted.

For comparison a 1% aqueous solution of the iodinepolyvinyl pyrrolidonecomposition utilized above, i. e. prior to blending with sodiumbicarbonate (having a pH of 2) and adjusted by the addition of anhydroussodium bicarbonate to a pH of 6.6 to 6.7, the amount of bicarbonateadded was not calculated, but made with vigorous stirring with the pHmetered electrodes immersed in the solution. In aging this solution at100 F. for six weeks, the pH increased from 6.6 to 7.4 and the availableiodine content decreased from 11.84 to 11.3%, and the iodide contentincreased from 3.9 to 4.51%.

By blending sodium bicarbonate with the iodine-polyvinyl pyrrolidonecomposition, the resulting blend may be packaged as one stable unit andimmediately utilized without further compounding. This expedient saves aconsiderable amount of money in packaging and shipping.

I claim:

The method of forming an aqueous iodine-polyvinylpyrrolidone compositionwhich is stable with respect to a change in pH and loss in availableiodine content, which comprises blending anhydrous sodium bicarbonatewith dry iodine-polyvinyl-pyrrolidone composition until a uniformmixture is obtained, and dissolving the said mixture in water.

References Cited in the file of this patent UNITED STATES PATENTS OTHERREFERENCES Chemical Week, 69:25, Dec. 22, 1951, p. 19.

C and E N (Chem. and Eng. News), Feb. 19, 1951,

p. 664, New Iodine Compound.

Ridge et al.: Control of pH in Bleaching, Textile Manufacturer, July1942, p. 282.

